This retrospective cohort study characterizes how interest in science, technology, engineering, mathematics (STEM) careers changes during high school for more than 6,000 students in a representative national sample of 34 two- and four-year colleges taking mandatory college English courses. Overall, large gender differences in career plans were found, with males showing far more interest particularly in engineering, whereas females were more attracted to careers in health and medicine during their high school years. The key factor predicting STEM career interest at the end of high school was interest at the start of high school. There was an additional effect of gender, indicating both a lower retention of STEM career interest among females and a greater difficulty in attracting females to STEM fields during high school. During the high school years, the percentage of males interested in a STEM career remained stable (from 39.5 to 39.7), whereas for females it declined from 15.7 to 12.7. The students' initial specific (disciplinary) career interests were found to influence the stability of their interest in a STEM career, with those interested in physics careers at the start of high school having the highest retention in STEM.